rs890832

Variant names:

• chr5-151890769-G-A
• rs890832
• NM_000171.4:c.184+1542C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151890769-G-A
• chr5-151890769-G-C
• chr5-151890769-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000171.4(GLRA1):​c.184+1542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,082 control chromosomes in the GnomAD database, including 43,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (43864 hom., cov: 31)
• Consequence: GLRA1 NM_000171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 6 publications found

Genes affected

GLRA1 (HGNC:4326): (glycine receptor alpha 1) The protein encoded by this gene is a subunit of a pentameric inhibitory glycine receptor, which mediates postsynaptic inhibition in the central nervous system. Defects in this gene are a cause of startle disease (STHE), also known as hereditary hyperekplexia or congenital stiff-person syndrome. Multiple transcript variants encoding different isoforms have been found. [provided by RefSeq, Dec 2015]

GLRA1 Gene-Disease associations (from GenCC):

• hyperekplexia 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA1	NM_000171.4	c.184+1542C>T		intron_variant	Intron 2 of 8	ENST00000274576.9	NP_000162.2
GLRA1	NM_001146040.2	c.184+1542C>T		intron_variant	Intron 2 of 8		NP_001139512.1
GLRA1	NM_001292000.2	c.-65-3981C>T		intron_variant	Intron 1 of 7		NP_001278929.1
GLRA1	XM_047417105.1	c.232+1542C>T		intron_variant	Intron 2 of 8		XP_047273061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA1	ENST00000274576.9	c.184+1542C>T		intron_variant	Intron 2 of 8	1	NM_000171.4	ENSP00000274576.5
GLRA1	ENST00000455880.2	c.184+1542C>T		intron_variant	Intron 2 of 8	1		ENSP00000411593.2
GLRA1	ENST00000462581.6	n.57-3981C>T		intron_variant	Intron 1 of 7	1		ENSP00000430595.1
GLRA1	ENST00000471351.2	n.467+1542C>T		intron_variant	Intron 2 of 7	1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115033 AN: 151964 Hom.: 43812 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.757 AC: 115141 AN: 152082 Hom.: 43864 Cov.: 31 AF XY: 0.761 AC XY: 56527 AN XY: 74318

African (AFR) AF: 0.781 AC: 32395 AN: 41466

American (AMR) AF: 0.798 AC: 12209 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2571 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4793 AN: 5176

South Asian (SAS) AF: 0.868 AC: 4178 AN: 4814

European-Finnish (FIN) AF: 0.729 AC: 7700 AN: 10558

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48867 AN: 67992

Other (OTH) AF: 0.744 AC: 1570 AN: 2110

Alfa AF: 0.730 Hom.: 68357

Bravo AF: 0.763

Asia WGS AF: 0.875 AC: 3040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.24
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs890832; hg19: chr5-151270330;